Cancer of the cervix is the third most common cancer in women worldwide and the greatest cancer killer of women in the developing world. Of the estimated 600 women who die each day of cervical cancer, 80% are from the third world where access to adequate cancer screening and therapeutic interventions is limited. Yet we know that all women, who have access to and utilize screening, can be diagnosed and cured at the early stages of cervical intraepithelial neoplasia (CIN). Human Papilloma Virus (HPV) oncogenic subtypes are recognized as the cause of cervical cancer and the Pap smear has been the mainstay of cervical cancer screening. The Pap smear however requires many practical and technical considerations, including: 1) accessibility to health care providers with the necessary skills to perform the specimen collection; 2) trained cytopathologists to evaluate the slides; and 3) a recall system to promptly notify and re-evaluate patients with abnormal results. In rural China, women are not screened for cervical cancer and do not have access to health care providers trained to collect specimens and evaluate them. Indeed, the 1990-1992 age-standardized cervical cancer mortality rates in China were 3.84/100,000 and the highest rates occurred in Shanxi Province (12.4/100,000). Therefore a team of investigators from the Cleveland Clinic, Ohio and from the Cancer Institute, Chinese Academy of Medical Sciences (CICAMS), Beijing, China in collaboration with the National Cancer Institute (CCR) designed a study to compare the sensitivity and specificity of a self-test for HPV in contrast with the direct HPV test among women who have never been screened in Shanxi Province. As part of this overall study, I was responsible for development of an epidemiology and nutritional questionnaire to assess recognized reproductive risk factors and explore the role of diet, infection and family history of cancer on risk of HPV positivity, CIN, and invasive cervical cancer. After completing a pilot study to evaluate the culture-specific dietary food frequency questionnaire, the first (SPOCCS I) of two main studies was completed in 1997 women aged 35-50 years, who were selected from all women in select villages in Shanxi Province in 1999. The study design included an initial session to train women how to collect a cervical specimen using the HPV self-test, followed by the actual specimen collection. Approximately 4 to 12 months later, the women returned for clinical assessment and a fasting blood draw as well as an interviewer-administered epidemiology and dietary food frequency questionnaire. A similarly designed study (SPOCCS II) was conducted in 2002 on 9183 women of the same age range, who were selected from the Province. Research AimsAs part of a study of the sensitivity and specificity of HPV self-test in an unscreened population of women aged 35-50 y, the overall aims are to examine the relation of nutritional status, immunological conditions, and their interaction on risk of the following: HPV +, persistent HPV +, CIN I, II, III and invasive cervical cancer. Specific hypotheses relate to the role of dietary intake of fruits and vegetables rich in folate, isothiocyanates, and other micronutrients with chemopreventive potential and risk of the abovementioned endpoints, while other hypotheses relate to the role of infections as well as the interaction of nutritional status and immunological status on risk.